scholarly journals Characterization of Plasmids in Extensively Drug-Resistant Acinetobacter Strains Isolated in India and Pakistan

2014 ◽  
Vol 59 (2) ◽  
pp. 923-929 ◽  
Author(s):  
Lim S. Jones ◽  
Maria J. Carvalho ◽  
Mark A. Toleman ◽  
P. Lewis White ◽  
Thomas R. Connor ◽  
...  
Keyword(s):  
Selection Pressure ◽  
Gram Negative Bacteria ◽  
Drug Resistant ◽  
Content Type ◽  
Extensively Drug Resistant ◽  
Extensive Drug Resistance ◽  
Acinetobacter Haemolyticus ◽  
Insight Into

ABSTRACTTheblaNDM-1gene is associated with extensive drug resistance in Gram-negative bacteria. This probably spread toEnterobacteriaceaefromAcinetobacterspp., and we characterized plasmids associated withblaNDM-1inAcinetobacterspp. to gain insight into their role in this dissemination. Four clinical NDM-1-producingAcinetobacterspecies strains from India and Pakistan were investigated. A plasmid harboringblaNDM-1, pNDM-40-1, was characterized by whole-genome sequencing ofAcinetobacter bereziniaeCHI-40-1 and comparison with related plasmids. The presence of similar plasmids in strains from Pakistan was sought by PCR and sequencing of amplicons. Conjugation frequency was tested and stability of pNDM-40-1 investigated by real-time PCR of isolates passaged with and without antimicrobial selection pressure.A. bereziniaeandAcinetobacter haemolyticusstrains contained plasmids similar to the pNDM-BJ01-like plasmids identified inAcinetobacterspp. in China. The backbone of pNDM-40-1 was almost identical to that of pNDM-BJ01-like plasmids, but the transposon harboringblaNDM-1, Tn125, contained two short deletions.Escherichia coliandAcinetobacterpittiitransconjugants were readily obtained. Transconjugants retained pNDM-40-1 after a 14-day passage experiment, although stability was greater with meropenem selection. Fragments of pNDM-BJ01-like plasmid backbones are found nearblaNDM-1in some genetic contexts fromEnterobacteriaceae, suggesting that cross-genus transfer has occurred. pNDM-BJ01-like plasmids have been described in isolates originating from a wide geographical region in southern Asia.In vitrodata on plasmid transfer and stability suggest that these plasmids could have contributed to the spread ofblaNDM-1intoEnterobacteriaceae.

scholarly journals Comparison of In Vitro Activity and MIC Distributions between the Novel Oxazolidinone Delpazolid and Linezolid against Multidrug-Resistant and Extensively Drug-Resistant Mycobacterium tuberculosis in China

2018 ◽  
Vol 62 (8) ◽  
Author(s):  
Zhaojing Zong ◽  
Wei Jing ◽  
Jin Shi ◽  
Shu'an Wen ◽  
Tingting Zhang ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Novel Mutation ◽  
Multidrug Resistant ◽  
23S Rrna ◽  
Drug Resistant ◽  
Content Type ◽  
Extensively Drug Resistant ◽  
Significant Difference ◽  
Mdr Tb

ABSTRACT Oxazolidinones are efficacious in treating mycobacterial infections, including tuberculosis (TB) caused by drug-resistant Mycobacterium tuberculosis. In this study, we compared the in vitro activities and MIC distributions of delpazolid, a novel oxazolidinone, and linezolid against multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) in China. Additionally, genetic mutations in 23S rRNA, rplC, and rplD genes were analyzed to reveal potential mechanisms underlying the observed oxazolidinone resistance. A total of 240 M. tuberculosis isolates were included in this study, including 120 MDR-TB isolates and 120 XDR-TB isolates. Overall, linezolid and delpazolid MIC90 values for M. tuberculosis isolates were 0.25 mg/liter and 0.5 mg/liter, respectively. Based on visual inspection, we tentatively set epidemiological cutoff (ECOFF) values for MIC determinations for linezolid and delpazolid at 1.0 mg/liter and 2.0 mg/liter, respectively. Although no significant difference in resistance rates was observed between linezolid and delpazolid among XDR-TB isolates (P > 0.05), statistical analysis revealed a significantly greater proportion of linezolid-resistant isolates than delpazolid-resistant isolates within the MDR-TB group (P = 0.036). Seven (53.85%) of 13 linezolid-resistant isolates were found to harbor mutations within the three target genes. Additionally, 1 isolate exhibited an amino acid substitution (Arg126His) within the protein encoded by rplD that contributed to high-level resistance to linezolid (MIC of >16 mg/liter), compared to a delpazolid MIC of 0.25. In conclusion, in vitro susceptibility testing revealed that delpazolid antibacterial activity was comparable to that of linezolid. A novel mutation within rplD that endowed M. tuberculosis with linezolid, but not delpazolid, resistance was identified.

scholarly journals Antimicrobial Activity of Ceftazidime-Avibactam Tested against Multidrug-Resistant Enterobacteriaceae and Pseudomonas aeruginosa Isolates from U.S. Medical Centers, 2013 to 2016

2017 ◽  
Vol 61 (11) ◽  
Author(s):  
Helio S. Sader ◽  
Mariana Castanheira ◽  
Dee Shortridge ◽  
Rodrigo E. Mendes ◽  
Robert K. Flamm
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Multidrug Resistant ◽  
Drug Resistant ◽  
Large Collection ◽  
Content Type ◽  
Negative Results ◽  
Medical Centers ◽  
Extensively Drug Resistant ◽  
Genes Encoding

ABSTRACT The in vitro activity of ceftazidime-avibactam and many comparator agents was determined against various resistant subsets of organisms selected among 36,380 Enterobacteriaceae and 7,868 Pseudomonas aeruginosa isolates. The isolates were consecutively collected from 94 U.S. hospitals, and all isolates were tested for susceptibility by reference broth microdilution methods in a central monitoring laboratory (JMI Laboratories). Enterobacteriaceae isolates resistant to carbapenems (CRE) and/or ceftazidime-avibactam (MIC ≥ 16 μg/ml) were evaluated for the presence of genes encoding extended-spectrum β-lactamases and carbapenemases. Ceftazidime-avibactam inhibited >99.9% of all Enterobacteriaceae at the susceptible breakpoint of ≤8 μg/ml and was active against multidrug-resistant (MDR; n = 2,953; MIC50/90, 0.25/1 μg/ml; 99.2% susceptible), extensively drug-resistant (XDR; n = 448; MIC50/90, 0.5/2 μg/ml; 97.8% susceptible), and CRE (n = 513; MIC50/90, 0.5/2 μg/ml; 97.5% susceptible) isolates. Only 82.2% of MDR Enterobacteriaceae (n = 2,953) and 64.2% of ceftriaxone-nonsusceptible Klebsiella pneumoniae (n = 1,063) isolates were meropenem susceptible. Among Enterobacter cloacae (22.2% ceftazidime nonsusceptible), 99.8% of the isolates, including 99.3% of the ceftazidime-nonsusceptible isolates, were ceftazidime-avibactam susceptible. Only 23 of 36,380 Enterobacteriaceae (0.06%) isolates were ceftazidime-avibactam nonsusceptible, including 9 metallo-β-lactamase producers and 2 KPC-producing strains with porin alteration; the remaining 12 strains showed negative results for all β-lactamases tested. Ceftazidime-avibactam showed potent activity against P. aeruginosa (MIC50/90, 2/4 μg/ml; 97.1% susceptible), including MDR (MIC50/90, 4/16 μg/ml; 86.5% susceptible) isolates, and inhibited 71.8% of isolates nonsusceptible to meropenem, piperacillin-tazobactam, and ceftazidime (n = 628). In summary, ceftazidime-avibactam demonstrated potent activity against a large collection (n = 44,248) of contemporary Gram-negative bacilli isolated from U.S. patients, including organisms resistant to most currently available agents, such as CRE and meropenem-nonsusceptible P. aeruginosa.

scholarly journals Correlation of Checkerboard Synergy Testing with Time-Kill Analysis and Clinical Outcomes of Extensively Drug-Resistant Acinetobacter baumannii Respiratory Infections

2016 ◽  
Vol 60 (11) ◽  
pp. 6892-6895 ◽  
Author(s):  
Derek N. Bremmer ◽  
Karri A. Bauer ◽  
Stephanie M. Pouch ◽  
Keelie Thomas ◽  
Debra Smith ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Clinical Outcomes ◽  
Clinical Utility ◽  
Respiratory Infections ◽  
Drug Resistant ◽  
Content Type ◽  
Extensively Drug Resistant ◽  
Time Kill ◽  
Synergy Testing

ABSTRACTWe tested 76 extensively drug-resistant (XDR)Acinetobacter baumanniiisolates by the checkerboard method using only wells containing serum-achievable concentrations (SACs) of drugs. Checkerboard results were correlated by time-kill assay and clinical outcomes. Minocycline-colistin was the best combinationin vitro, as it inhibited growth in one or more SAC wells in all isolates. Patients who received a combination that inhibited growth in one or more SAC wells demonstrated better microbiological clearance than those who did not (88% versus 30%;P= 0.025). The checkerboard platform may have clinical utility for XDRA. baumanniiinfections.

scholarly journals A Genotype-Phenotype Correlation Study of SHV β-Lactamases Offers New Insight into SHV Resistance Profiles

2020 ◽  
Vol 64 (7) ◽  
Author(s):  
Svetlana Neubauer ◽  
Sara Madzgalla ◽  
Mike Marquet ◽  
Anne Klabunde ◽  
Bernd Büttner ◽  
...  
Keyword(s):  
Correlation Study ◽  
Gram Negative Bacteria ◽  
Promoter Mutation ◽  
Phenotype Correlation ◽  
Content Type ◽  
Substrate Specificities ◽  
Third Generation Cephalosporins ◽  
Insight Into ◽  
Lactamase Inhibitor

ABSTRACT The SHV β-lactamases (BLs) have undergone strong allele diversification that has changed their substrate specificities. Based on 147 NCBI entries for SHV alleles, in silico mathematical models predicted 5 positions as relevant for the β-lactamase inhibitor (BLI)-resistant (2br) phenotype, 12 positions as relevant for the extended-spectrum BL (ESBL) (2be) phenotype, and 2 positions as related solely to the narrow-spectrum (2b) phenotype. These positions and six additional positions described in other studies (including one promoter mutation) were systematically substituted and investigated for their substrate specificities in a BL-free Escherichia coli background, representing, to our knowledge, the most comprehensive substrate and substitution analysis for SHV alleles to date. An in vitro analysis confirmed the essentiality of positions 238 and 179 for the 2be phenotype and of position 69 for the 2br phenotype. The E240K and E240R substitutions, which do not occur alone in known 2br SHV variants, led to a 2br phenotype, indicating a latent BLI resistance potential of these substitutions. The M129V, A234G, S271I, and R292Q substitutions conferred latent resistance to cefotaxime. In addition, seven positions that were found not always to be associated with the ESBL phenotype resulted in increased resistance to ceftaroline. We also observed that coupling of a strong promoter (IS26) to an A146V mutant with the 2b phenotype resulted in highly increased resistance to BLIs, cefepime, and ceftaroline but not to third-generation cephalosporins, indicating that SHV enzymes represent an underestimated risk for empirical therapies that use piperacillin-tazobactam or cefepime to treat different infectious diseases caused by Gram-negative bacteria.

scholarly journals Tridecaptin M, a New Variant Discovered in Mud Bacterium, Shows Activity against Colistin- and Extremely Drug-ResistantEnterobacteriaceae

2019 ◽  
Vol 63 (6) ◽  
Author(s):  
Manoj Jangra ◽  
Manpreet Kaur ◽  
Rushikesh Tambat ◽  
Rohit Rana ◽  
Sushil K. Maurya ◽  
...  
Keyword(s):  
Hemolytic Activity ◽  
World Health ◽  
Fourth Generation ◽  
Infection Model ◽  
Drug Resistant ◽  
Content Type ◽  
Extensively Drug Resistant ◽  
New Variant

ABSTRACTThe World Health Organization has categorized the Gram-negative superbugs, which are inherently impervious to many antibiotics, as critical priority pathogens due to the lack of effective treatments. The breach in our last-resort antibiotic (i.e., colistin) by extensively drug-resistant and pan-drug-resistantEnterobacteriaceaestrains demands the immediate development of new therapies. In the present study, we report the discovery of tridecaptin M, a new addition to the family, and its potential against colistin-resistantEnterobacteriaceae in vitroandin vivo. Also, we performed mode-of-action studies using various fluorescent probes and studied the hemolytic activity and mammalian cytotoxicity in two cell lines. Tridecaptin M displayed strong antibacterial activity (MICs of 2 to 8 μg ml−1) against clinical strains ofKlebsiella pneumoniae(which were resistant to colistin, carbapenems, third- and fourth-generation cephalosporins, fluoroquinolones, fosfomycin, and other antibiotics) andmcr-1-positiveEscherichia colistrains. Unlike polymyxins, tridecaptin M did not permeabilize the outer membrane or cytoplasmic membrane. It blocked ATP synthesis in bacteria by dissipating the proton motive force. The compound exhibited negligible acquired resistance, lowin vitrocytotoxicity and hemolytic activity, and no significant acute toxicity in mice. It also showed promising efficacy in a thigh infection model of colistin-resistantK. pneumoniae. Altogether, these results demonstrate the future prospects of this class of antibiotics to address the unmet medical need to circumvent colistin resistance in extensively drug-resistantEnterobacteriaceaeinfections. The work also emphasizes the importance of natural products in our shrunken drug discovery pipeline.

scholarly journals In Vitro Activity and MIC of Sitafloxacin against Multidrug-Resistant and Extensively Drug-Resistant Mycobacterium tuberculosis Isolated in Thailand

2017 ◽  
Vol 62 (1) ◽  
Author(s):  
Manoon Leechawengwongs ◽  
Therdsak Prammananan ◽  
Sarinya Jaitrong ◽  
Pamaree Billamas ◽  
Nampueng Makhao ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Critical Concentration ◽  
Multidrug Resistant ◽  
Quinolone Resistance ◽  
Drug Resistant ◽  
Content Type ◽  
Extensively Drug Resistant ◽  
Resistant Strains ◽  
Drug Resistant Strains

ABSTRACT New fluoroquinolones (FQs) have been shown to be more active against drug-resistant Mycobacterium tuberculosis strains than early FQs, such as ofloxacin. Sitafloxacin (STFX) is a new fluoroquinolone with in vitro activity against a broad range of bacteria, including M. tuberculosis. This study aimed to determine the in vitro activity of STFX against all groups of drug-resistant strains, including multidrug-resistant M. tuberculosis (MDR M. tuberculosis), MDR M. tuberculosis with quinolone resistance (pre-XDR), and extensively drug-resistant (XDR) strains. A total of 374 drug-resistant M. tuberculosis strains were tested for drug susceptibility by the conventional proportion method, and 95 strains were randomly submitted for MIC determination using the microplate alamarBlue assay (MABA). The results revealed that all the drug-resistant strains were susceptible to STFX at a critical concentration of 2 μg/ml. Determination of the MIC90s of the strains showed different MIC levels; MDR M. tuberculosis strains had a MIC90 of 0.0625 μg/ml, whereas pre-XDR and XDR M. tuberculosis strains had identical MIC90s of 0.5 μg/ml. Common mutations within the quinolone resistance-determining region (QRDR) of gyrA and/or gyrB did not confer resistance to STFX, except that double mutations of GyrA at Ala90Val and Asp94Ala were found in strains with a MIC of 1.0 μg/ml. The results indicated that STFX had potent in vitro activity against all the groups of drug-resistant M. tuberculosis strains and should be considered a new repurposed drug for treatment of multidrug-resistant and extensively drug-resistant TB.

scholarly journals Trends in the Susceptibility of Clinically Important Resistant Bacteria to Tigecycline: Results from the TigecyclineIn VitroSurveillance in Taiwan Study, 2006 to 2010

2011 ◽  
Vol 56 (3) ◽  
pp. 1452-1457 ◽  
Author(s):  
Yen-Hsu Chen ◽  
Po-Liang Lu ◽  
Cheng-Hua Huang ◽  
Chun-Hsing Liao ◽  
Chin-Te Lu ◽  
...  
Keyword(s):  
Resistant Bacteria ◽  
Gram Negative Bacteria ◽  
Drug Resistant ◽  
Content Type ◽  
E Coli ◽  
Drug Resistant Bacteria ◽  
Vancomycin Resistant ◽  
Susceptibility Rate ◽  
Important Drug

ABSTRACTThe TigecyclineIn VitroSurveillance in Taiwan (TIST) study, a nationwide, prospective surveillance during 2006 to 2010, collected a total of 7,793 clinical isolates, including methicillin-resistantStaphylococcus aureus(MRSA) (n= 1,834), penicillin-resistantStreptococcus pneumoniae(PRSP) (n= 423), vancomycin-resistant enterococci (VRE) (n= 219), extended-spectrum β-lactamase (ESBL)-producingEscherichia coli(n= 1,141), ESBL-producingKlebsiella pneumoniae(n= 1,330),Acinetobacter baumannii(n= 1,645), andStenotrophomonas maltophilia(n= 903), from different specimens from 20 different hospitals in Taiwan. MICs of tigecycline were determined following the criteria of the U.S. Food and Drug Administration (FDA) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST-2011). Among drug-resistant Gram-positive pathogens, all of the PRSP isolates were susceptible to tigecycline (MIC90, 0.03 μg/ml), and only one MRSA isolate (MIC90, 0.5 μg/ml) and three VRE isolates (MIC90, 0.125 μg/ml) were nonsusceptible to tigecycline. Among the Gram-negative bacteria, the tigecycline susceptibility rates were 99.65% for ESBL-producingE. coli(MIC90, 0.5 μg/ml) and 96.32% for ESBL-producingK. pneumoniae(MIC90, 2 μg/ml) when interpreted by FDA criteria but were 98.7% and 85.8%, respectively, when interpreted by EUCAST-2011 criteria. The susceptibility rate forA. baumannii(MIC90, 4 μg/ml) decreased from 80.9% in 2006 to 55.3% in 2009 but increased to 73.4% in 2010. A bimodal MIC distribution was found among carbapenem-susceptibleA. baumanniiisolates, and a unimodal MIC distribution was found among carbapenem-nonsusceptibleA. baumanniiisolates. In Taiwan, tigecycline continues to have excellentin vitroactivity against several major clinically important drug-resistant bacteria, with the exception ofA. baumannii.

scholarly journals Tebipenem as an oral alternative for the treatment of typhoid caused by extensively drug resistant (XDR) Salmonella Typhi

2021 ◽  
Author(s):  
Elli Mylona ◽  
Phat Voong Vinh ◽  
Sonia Qureshi ◽  
Abhilasha Karkey ◽  
Sabina Dongol ◽  
...  
Keyword(s):  
Enteric Fever ◽  
Salmonella Typhi ◽  
Drug Resistant ◽  
Extensively Drug Resistant ◽  
Extensive Drug Resistance ◽  
Spectrum Activity ◽  
Fever Treatment ◽  
Emergence Of Resistance ◽  
Broad Spectrum Activity

Abstract The emergence of multi-drug (MDR) and extensive-drug resistance (XDR) in Salmonella Typhi and Paratyphi A hinder efficacious out-patient enteric fever treatment. We show that non-XDR and XDR S. Typhi and S. Paratyphi A are susceptible to the carbapenem tebipenem in vitro. Tebipenem demonstrated partial synergy with antimicrobials including azithromycin, signifying combination therapy may limit the emergence of resistance. Given recent evidence on tebipenem inhibitory activity against MDR Shigella, its broad-spectrum activity against MDR/XDR organisms renders it a good clinical trial candidate.

scholarly journals Two Novel Bacteriophages Improve Survival in Galleria mellonella Infection and Mouse Acute Pneumonia Models Infected with Extensively Drug-Resistant Pseudomonas aeruginosa

2019 ◽  
Vol 85 (9) ◽  
Author(s):  
Jongsoo Jeon ◽  
Dongeun Yong
Keyword(s):  
Pseudomonas Aeruginosa ◽  
In Silico ◽  
Galleria Mellonella ◽  
Drug Resistant ◽  
Content Type ◽  
Bacteriolytic Activity ◽  
Extensively Drug Resistant ◽  
Acute Pneumonia

ABSTRACT Extensively drug-resistant Pseudomonas aeruginosa (XDR-PA) is a life-threatening pathogen that causes serious global problems. Here, we investigated two novel P. aeruginosa bacteriophages (phages), Bϕ-R656 and Bϕ-R1836, in vitro, in silico, and in vivo to evaluate the potential of phage therapy to control XDR-PA clinical strains. Bϕ-R656 and Bϕ-R1836 belong to the Siphoviridae family and exhibited broad host ranges which could lyse 18 (64%) and 14 (50%) of the 28 XDR-PA strains. In addition, the two phages showed strong bacteriolytic activity against XDR-PA host strains from pneumonia patients. The whole genomes of Bϕ-R656 and Bϕ-R1836 have linear double-stranded DNA of 60,919 and 37,714 bp, respectively. The complete sequence of Bϕ-R656 had very low similarity to the previously discovered P. aeruginosa phages in GenBank, but phage Bϕ-R1836 exhibited 98% and 91% nucleotide similarity to Pseudomonas phages YMC12/01/R24 and PA1/KOR/2010, respectively. In the two in vivo infection models, treatment with Bϕ-R656 and Bϕ-R1836 enhanced the survival of Galleria mellonella larvae (50% and 60%, respectively) at 72 h postinfection and pneumonia-model mice (66% and 83%, respectively) at 12 days postinfection compared with untreated controls. Treatment with Bϕ-R656 or Bϕ-R1836 also significantly decreased the bacterial load in the lungs of the mouse pneumonia model (>6 log10 CFU and >4 log10 CFU, respectively) on day 5. IMPORTANCE In this study, two novel P. aeruginosa phages, Bϕ-R656 and Bϕ-R1836, were evaluated in vitro, in silico, and in vivo for therapeutic efficacy and safety as an alternative antibacterial agent to control XDR-PA strains collected from pneumonia patients. Both phages exhibited potent bacteriolytic activity and greatly improved survival in G. mellonella larva infection and a mouse acute pneumonia model. Based on these results, we strongly predict that these two new phages could be used as fast-acting and safe alternative biological weapons against XDR-PA infections.

scholarly journals Draft Genome Sequence of the Extensively Drug-Resistant Pseudomonas aeruginosa Clinical Isolate TUEPA7472

2018 ◽  
Vol 7 (12) ◽  
Author(s):  
Henrike Miess ◽  
Ghazaleh Jahanshah ◽  
Heike Brötz-Oesterhelt ◽  
Matthias Willmann ◽  
Silke Peter ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Genome Sequence ◽  
Draft Genome ◽  
Resistance Mechanisms ◽  
Draft Genome Sequence ◽  
Drug Resistant ◽  
Gram Negative ◽  
Content Type ◽  
Extensively Drug Resistant ◽  
Insight Into

Pseudomonas aeruginosa TUEPA7472 is extensively drug resistant (XDR) and is a representative Gram-negative rod that is multiresistant toward 4 classes of clinically relevant antibiotics (4MRGN). The 6.8-Mb draft genome sequence of this strain provides insight into these resistance mechanisms and the potential of the strain to produce virulence factors.

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